Compositions for protection against superficial vasodilator flush syndrome, and methods of use

Abstract

Compositions for protection against SVFS induced by niacin, a carcinoid, mesenteric traction, serotonin, post-menopause, alcohol, monosodium glutamate, mastocytosis, atopic dermatitis, food-allergy or food intolerance, and mast cell activation syndrome, or against individual symptoms of SVFS, superficial vasodilation, feeling of warmth, itching (pruritus) and hives, comprising a flavonoid compound of the structure 2-phenyl-4H-1-benzopyran or 2-phenyl-4-keto-1-benzopyran or glycosides thereof, or chalconoid compounds, with appropriate substitutions of their hydroxyl groups to render them water soluble or in combination with a pshospholipid or cyclodextrin to render them to have higher oral absorption, administered alone or together with an anti-superficial vasodilation dose of one or more of, olive kernel oil, a serotonin inhibitor, a prostaglandin inhibitor, willow bark extract. A composition for treating cardiovascular disease with niacin, but without eliciting the SVFS effects of niacin, has also been invented.

1 . A pharmaceutical composition for protecting humans against superficial vasodilator flush syndrome (“SVFS”) comprising a flavonoid compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein X is carbonyl, O-Z, Y, or H; 
         each Y is independently H, O-Z, or a halogen; 
         Z is H, alkali metal, or alkali earth metal; 
         or a glycoside thereof. 
       
     
     
         2 . The composition of  claim 1 , wherein said flavonoid compound is selected from the group consisting of luteolin, quercetin, myricetin, genistein, curcumin, epigallocatechin or a glycoside derivative of said flavonoids. 
     
     
         3 . The composition of  claim 1 , wherein the flavonoid is formulated together with a phospholipid or cyclodextran to increase oral absorption. 
     
     
         4 . The composition of  claim 1 , wherein said composition contains a composition that lowers total serum cholesterol or LDL cholesterol. 
     
     
         5 . The composition of  claim 4 , wherein the cholesterol-lowering composition is a statin. 
     
     
         6 . The composition of  claim 5 , wherein said statin is selected from the group consisting of simvastatin, I-vastatin, atorvastatin, rosuvastatin, fluvastatin, and provastatin. 
     
     
         7 . The composition of  claim 1 , wherein said composition comprises of a compound that increases serum HDL cholesterol. 
     
     
         8 . The composition of  claim 1 , wherein the composition contains a prostaglandin inhibitor. 
     
     
         9 . The composition of  claim 8 , wherein the prostaglandin inhibitor is selected from the group consisting of non-steroidal anti-inflammatory drugs, COX-2 inhibitors, PGD 2  antagonist, and corticosteroids. 
     
     
         10 . The composition of  claim 9 , wherein the PGD2 antagonist is laropiprant. 
     
     
         11 . The composition of  claim 1 , wherein said flavonoid composition is supplemented with one or more additional anti-SVFS compounds. 
     
     
         12 . The composition of  claim 11 , wherein said supplemental anti-SVFS compound is a serotonin inhibitor. 
     
     
         13 . The composition of  claim 12 , wherein said inhibitor is a serotonin receptor antagonist. 
     
     
         14 . The composition of  claim 13 , wherein said antagonist is prochlorperazine or ketanserin. 
     
     
         15 . The composition of  claim 13 , wherein said serotonin inhibitor is a mixed histamine-1 and serotonin receptor antagonist selected from the group consisting of cyproheptadine or azatadine. 
     
     
         16 . A pharmaceutical composition for protecting humans against superficial vasodilator flush syndrome (“SVFS”) comprising a chalconoid compound of Formula II: 
       
         
           
           
               
               
           
         
         wherein each Y is independently H, O-Z, or a halogen; 
         Z is H, alkali metal, or alkali earth metal; 
         or a glycoside thereof. 
       
     
     
         17 . The composition of  claim 16 , wherein said flavonoid compound is selected from the group consisting of luteolin, quercetin, myricetin, genistein, curcumin, epigallocatechin or a glycoside derivative of said flavonoids. 
     
     
         18 . The composition of  claim 16 , wherein the flavonoid is formulated together with a phospholipid or cyclodextran to increase oral absorption. 
     
     
         19 . The composition of  claim 16 , wherein said composition contains a composition that lowers total serum cholesterol or LDL cholesterol. 
     
     
         20 . The composition of  claim 19 , wherein the cholesterol-lowering composition is a statin. 
     
     
         21 . The composition of  claim 20 , wherein said statin is selected from the group consisting of simvastatin, I-vastatin, atorvastatin, rosuvastatin, fluvastatin, and provastatin. 
     
     
         22 . The composition of  claim 16 , wherein said composition comprises of a compound that increases serum HDL cholesterol. 
     
     
         23 . The composition of  claim 16 , wherein the composition contains a prostaglandin inhibitor. 
     
     
         24 . The composition of  claim 23 , wherein the prostaglandin inhibitor is selected from the group consisting of non-steroidal anti-inflammatory drugs, COX-2 inhibitors, PGD 2  antagonist, and corticosteroids. 
     
     
         25 . The composition of  claim 24 , wherein the PGD2 antagonist is Laropiprant. 
     
     
         26 . The composition of  claim 16 , wherein said flavonoid composition is supplemented with one or more additional anti-SVFS compounds. 
     
     
         27 . The composition of  claim 26 , wherein said supplemental anti-SVFS compound is a serotonin inhibitor. 
     
     
         28 . The composition of  claim 27 , wherein said inhibitor is a serotonin receptor antagonist. 
     
     
         29 . The composition of  claim 28 , wherein said antagonist is prochlorperazine or ketanserin. 
     
     
         30 . The composition of  claim 29 , wherein said serotonin inhibitor is a mixed histamine-1 and serotonin receptor antagonist selected from the group consisting of cyproheptadine or azatadine. 
     
     
         31 . A method for protecting an individual from the SVFS effects induced by niacin intake comprising administration to said individual effective doses for effective periods of time a composition of any one or more of  claims 1  or  16 . 
     
     
         32 . A method for protecting an individual from SVFS-associated symptoms of superficial vasodilation, feeling of warmth, itching (pruritus) and hives comprising administration to said individual effective doses for effective periods of time a composition of any one or more of  claims 1  or  16 . 
     
     
         33 . A method for protecting an individual from the SVFS effects associated with carcinoid-associated flush, mesenteric traction-induced flush, serotonin-induced flush, post-menopausal-induced flush, alcohol-induced flush and monosodium glutamate-induced flush, mastocytosis-induced, atopic dermatitis-induced, food-allergy or food intolerance-induced, and mast cell activation syndrome-induced SVFS comprising administration to said individual effective doses for effective periods of time a composition of any one or more of  claims 1  or  16 . 
     
     
         34 . A method for treating a cardiovascular condition in a patient with niacin, but without eliciting the SVFS effect of said niacin, comprising the administration to said patient of clinically effective amounts of a composition of any one or more of  claims 1  or  16 .